title: Dihydrotestosterone alters urocortin levels in human umbilical vein endothelial cells.
abstract: Urocortin (UCN1) is a member of corticotrophin-releasing factor (CRF) family, which has been proven to participate in inflammation. Previous work showed that dihydrotestosterone (DHT) could promote the inflammatory process. Little is known about the effect of DHT on UCN1 expression. The aim of our study is to investigate the effects and underlying mechanisms of DHT on endothelial UCN1 expression in the absence and presence of induced inflammation. Therefore, we tested the alterations of endothelial UCN1 expression treated with DHT in the presence or absence of lipopolysaccharide (LPS). Our data showed that DHT alone decreased UCN1 levels, which were attenuated in the presence of the androgen receptor (AR) antagonist flutamide. Conversely, in the presence of LPS, DHT augmented the LPS-induced increase in UCN1 expression, which was, interestingly, not affected by flutamide. When cells were treated with DHT alone, AR was upregulated and translocated into the nuclei, which might repress UCN1 expression via a potential androgen-responsive element found in human CRF family promoter. In the presence of LPS, DHT did not influence AR expression and location while it increased toll-like receptor 4 expression and activation, which was not altered by flutamide. DHT enhanced LPS-induced p38MAPK, ERK1/2, and nuclear factor κB pathway activation, which may contribute to the elevated expression of UCN1. These data suggest that DHT differentially influences UCN1 levels under normal and inflammatory conditions in human umbilical vein endothelial cells, which involves AR-dependent and -independent mechanisms respectively.
authors.affiliation: Jiangsu Provincial Key Lab of Cardiovascular Diseases and Molecular Intervention, Department of Pharmacology, Nanjing Medical University, Nanjing 210029, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Wan
authors.forename: Chao
authors.initials: C
authors.lastname: Zhu
authors.forename: Rui
authors.initials: R
authors.lastname: Guo
authors.forename: Lai
authors.initials: L
authors.lastname: Jin
authors.forename: Yunxin
authors.initials: Y
authors.lastname: Liu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Shengnan
authors.initials: S
authors.lastname: Li
mesh_terms: D000728:Androgens / Q000378:metabolism*; D013196:Dihydrotestosterone / Q000378:metabolism*; D005786:Gene Expression Regulation; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D054832:Urocortins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000728:Androgens; D008070:Lipopolysaccharides; D011944:Receptors, Androgen; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D054832:Urocortins; D013196:Dihydrotestosterone
keywords: androgen; inflammation; lipopolysaccharide; urocortin